miRNA biomarkers related to Alzheimer's disease (AD) that may be useful as a diagnostic tool or in elucidating the mechanisms of disease and discovery of novel therapeutics will be identified using a novel whole transcriptome qBead" X-MAP-based assay (not yet launched commercially). Biomarkers will be identified from brain formalin fixed (FFPE) tissue and matched serum samples of AD patients, patients diagnosed Parkinson's disease and dementia (PD), patients with cerebrovascular disease neuropathologically diagnosed as vascular dementia (VaD), and normal controls (NC). The results will be validated using matched frozen tissue and both the qBead assay and PCR. The qBead X-MAP assay utilizes the quantitative Nuclease Protection Assay (qNPA") and measures both miRNA and mRNA. It is very precise and sensitive. This program will exploit the qBead assay to validate the utility of FFPE and serum for identification of AD biomarkers, to confirm recent reports of altered miRNA levels in frozen brain of AD patients, and to provide an early example of an application of the qBead whole transcriptome miRNA assay. In Phase II mRNA biomarkers will be included and the studies expanded to a larger training set of AD, PD, VaD and NC FFPE, serum, buffy coat, and plasma samples to expand the biomarker set and then test an independent set of samples to confirm/validate the biomarkers. PUBLIC HEALTH RELEVANCE: miRNA biomarkers of Alzheimer's disease (AD) useful for diagnosis, for identifying mechanisms of disease, and as targets for drug discovery will be identified from brain FFPE and serum using a novel whole transcriptome qBead" X-MAP-based assay that has not yet been launched commercially. The qBead X-MAP assay utilizes the quantitative Nuclease Protection Assay (qNPA") and measures both miRNA and mRNA. It is very precise and sensitive and will enable the identification of low abundant miRNA and those that change by as little as 1.2-fold. Such small changes can be particularly relevant in tissues where a 1.2-fold change in a target population of cells making up only 40% of the sample may reflect a 50% change in those cells.